Kyrou et al. BMC Medicine(2020) 18:220
https://doi.org/10.1186/s12916-020-01697-5

OPINION

Open Access

Polycystic ovary syndrome (PCOS) and
COVID-19: an overlooked female patient
population at potentially higher risk during
the COVID-19 pandemic
Ioannis Kyrou1,2,3 , Emmanouil Karteris4, Tim Robbins1,5, Kamaljit Chatha6, Fotios Drenos4,7and Harpal S. Randeva1,2,3*

Abstract
Background: In women of reproductive age, polycystic ovary syndrome (PCOS) constitutes the most frequentendocrine disorder. Women with PCOS are considered to typically belong to an age and sex group which is at
lower risk for severe COVID-19.
Main body: Emerging data link the risk of severe COVID-19 with certain factors such as hyper-inflammation,
ethnicity predisposition, low vitamin D levels, and hyperandrogenism, all of which have known direct associations
with PCOS. Moreover, in this common female patient population, there is markedly high prevalence of multiple
cardio-metabolic conditions, such as type 2 diabetes, obesity, and hypertension, which may significantly increase
the risk for adverse COVID-19-related outcomes. This strong overlap of risk factors for both worse PCOS cardiometabolic manifestations and severe COVID-19 should be highlighted for the clinical practice, particularly since
women with PCOS often receive fragmented care from multiple healthcare services. Comprehensively informing
women with PCOS regarding the potential risks from COVID-19 and how this may affect their management is alsoessential.
Conclusion: Despite the immense challenges posed by the COVID-19 outbreak to the healthcare systems inaffected countries, attention should be directed to maintain a high standard of care for complex patients such as
many women with PCOS and provide relevant practical recommendations for optimal management in the settingof this fast moving pandemic.
Keywords: Polycystic ovary syndrome, PCOS, COVID-19, Severe acute respiratory syndrome coronavirus-2, SARSCoV-2, Diabetes, Obesity, Hypertension, Androgens, Vitamin D* Correspondence: Harpal.Randeva@warwick.ac.uk
1
Warwickshire Institute for the Study of Diabetes, Endocrinology andMetabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS
Trust, Coventry CV2 2DX, UK
2
Aston Medical Research Institute, Aston Medical School, Aston University,
Birmingham B4 7ET, UK
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Kyrou et al. BMC Medicine(2020) 18:220

BackgroundThe global outbreak of the new disease (COVID-19)
caused by the novel severe acute respiratory syndrome(SARS) coronavirus-2 (SARS-CoV-2) has reached pandemic status in March 2020 [1, 2]. Although asymptomatic or mild in most cases, COVID-19 may cause severe
illness with increased mortality in high-risk patients [3].
This has forced governments in affected countries to impose various degrees of quarantine and self-isolation
measures in order to reduce the COVID-19 incidence
and mortality [4]. An increasing body of clinical evidence indicates that the incidence of severe COVID-19
is significantly higher in older vs. younger adults and inmen vs. women [5–12]. Certain pre-existing comorbidities, including chronic cardio-metabolic diseases such as
diabetes, obesity, and hypertension, have also been
widely recognized as key risk factors for severe COVID19 [11, 13–17].
In women of reproductive age, polycystic ovary syndrome (PCOS) constitutes the most frequent endocrine
disorder with a prevalence which may reach or even exceed 10–15%, depending on the studied population andthe applied diagnostic criteria [18–20]. Following exclusion of related disorders (e.g., hyperprolactinemia,
hypothyroidism, and non-classic congenital adrenal
hyperplasia), both ovarian dysfunction (i.e., chronic
oligo- or anovulation) and hyperandrogenism (clinical,
i.e., hirsutism, and/or biochemical, i.e., increased freetestosterone or free androgen index) are the key featuresin order to establish the diagnosis of PCOS [18–20].
Polycystic ovary morphology on ultrasound has also
been introduced as another potential feature for diagnosing PCOS according to the Rotterdam PCOS diagnostic criteria [18–20]. Of note, despite the highprevalence of PCOS, its underlying etiology and pathophysiology are still not fully clarified, while PCOS management in routine clinical practice remains fragmented(e.g., between general practitioners, endocrinologists,and gynecologists), and with significant knowledge gaps
among physicians regarding the diagnosis, treatment,
and breadth of PCOS features [19–22]. As such, it is notuncommon for women with PCOS to fall between thegaps of relevant healthcare services even in the absenceof the extreme pressure applied to clinical practice by
the COVID-19 pandemic.
Overlap between common PCOS features andidentified risk factors for severe COVID-19
Cardio-metabolic comorbidity

PCOS is a complex and partly heterogeneous endocrine
disorder, often exhibiting a close association with obesity, insulin resistance, type 2 diabetes (T2DM), hypertension, dyslipidemia, obstructive sleep apnea (OSA), andnon-alcoholic fatty liver disease (NAFLD) [19, 23–25].

Page 2 of 10

Indeed, depending on the utilized PCOS definition andthe demographics of studied populations, up to 75% of
women with PCOS also have obesity, with increased central adiposity even independently of the underlying bodymass index (BMI) [19, 23]. This common PCOS phenotype is linked to heightened insulin resistance and hyperandrogenism; thus, women with PCOS exhibit markedly
increased prevalence of impaired glucose tolerance (IGT),
T2DM, and metabolic syndrome [19, 23, 24]. Overall,meta-analysis data suggest a 4-fold higher T2DM prevalence among women with PCOS which is both additiveand independent to obesity [26, 27]. As such, it is clearthat cardio-metabolic diseases which are common in
women with PCOS [19, 23, 24] exhibit significant overlap
with the risk factors predisposing to severe COVID-19(Fig. 1) [11, 13–17]. This overlap between the adverse
cardio-metabolic profile of women with PCOS and key
identified risk factors for worse clinical outcomes of
COVID-19 suggests that this common female patient
population is potentially at higher than expected risk if
confronted with a SARS-CoV-2 infection. Notably, in thecontext of the fragmented management of PCOS, superimposed comorbidities such as T2DM often “overshadow”
the underlying PCOS diagnosis in affected women; hence,
the latter should not be neglected when considering thecomorbidities in female COVID-19 patients, so that accurate characterization of the pre-existing risk profile of these
women is documented in relevant records/databases.
Hyperandrogenism

Compelling evidence indicates that, compared to
women, men exhibit higher predisposition to developing
severe COVID-19, independent of age [8, 12]. The molecular mechanisms which may facilitate this male predisposition for severe COVID-19 are currently
investigated, with particular focus placed on the role ofangiotensin-converting enzyme 2 (ACE-2) which is activated by the SARS-CoV-2 spike proteins and acts as oneof the key mediators for SARS-CoV-2 entry into hostcells [8, 28–30]. As such, attention is drawn on the potential effects of sex hormones on ACE-2 expression,
with animal data indicating that ACE-2 expression andactivity is influenced by sex hormones in various tissues,
such as the myocardium, adipose tissue, and kidneys [8].
Interestingly, a preliminary observation has been recently published regarding the high frequency of malepattern hair loss in hospitalized COVID-19 men, further
suggesting that androgens might be implicated in
COVID-19 severity [31]. Indeed, prompted by the evidence that male sex predisposes to severe COVID-19
and by the fact that male sex hormones impact on theACE-2 pathway which facilitates the entry of SARSCoV-2 into host cells [8, 28–30], Goren et al. documented that significant androgenic alopecia was a

Kyrou et al. BMC Medicine(2020) 18:220

Page 3 of 10

Fig. 1 Overlap between common factors which promote an unfavorable cardio-metabolic profile in women with polycystic ovary syndrome(PCOS) and factors which, based on the existing data, appear to increase the risk for severe COVID-19 (*further research is required to clarify thepotential links between adverse COVID-19-related outcomes and hyper-cytokinemia, hyperandrogenemia, and vitamin D deficiency)

common feature (71%) in a small cohort of hospitalized
male COVID-19 patients [n, 41; mean age (range), 58 (23–79) years] [31]. Accordingly, a potential association between
androgens and COVID-19 severity appears plausible andcould further support the hypothesis that anti-androgens
might represent an additional potential intervention against
severe COVID-19 [31–34]. This hypothesis also becomesrelevant in the context of PCOS, since women with PCOS
on one hand exhibit hyperandrogenism (e.g., androgenic
alopecia), while on the other hand may already be under
treatment with anti-androgens (e.g., spironolactone or finasteride) [19, 20, 35]. At the moment, there is a paucity ofdata regarding anti-androgen therapy in women with PCOS
in the context of COVID-19; hence, this is an additional aspect of the PCOS management which should be studied
during this pandemic. Of note, a male PCOS equivalent
syndrome has been proposed, which is characterized byearly-onset androgenic alopecia in combination with one ormore manifestations such as worse gonadal steroidogenesis,
decreased sex hormone binding globulin (SHBG), and increased dehydroepiandrosterone sulphate (DHEAS) circulating levels, as well as insulin resistance, T2DM, obesity,and hypertension [36, 37]. As such, there is a potential analogy between women with PCOS and a male PCOS

equivalent syndrome that are both linked to coexisting comorbidities (e.g., T2DM, obesity, and hypertension) which,as aforementioned, predispose to severe COVID-19.
However, it should be also noted that at the time ofwriting, there is a pre-print publication of a retrospective
study from Germany which reports that severe testosterone and dihydrotestosterone deficiencies were noted in asmall cohort of critically ill COVID-19 men [n, 35; median age (range), 62 (31–80) years] [38]. Moreover, inthe small number of female COVID-19 patients of thisstudy [n, 10; median age (range), 67.5 (54–84) years], apositive correlation was noted between testosterone
levels and pro-inflammatory cytokines (e.g., IL-6) [38].
As the publications, including pre-prints, of small cohort
studies on COVID-19 are increasing exponentially [39],it becomes clear that further systematic research is required to clarify the potential links between adverse
COVID-19 outcomes and factors such as circulating androgens in both male and female COVID-19 patients.
Hyper-inflammation

It is noteworthy that the severity of COVID-19 in certain
cases seems to also relate to predisposition for developing a cytokine storm syndrome with excessive release of

Kyrou et al. BMC Medicine(2020) 18:220

pro-inflammatory cytokines (e.g., tumor necrosis factorα, chemokines, and interleukins such as IL-6, IL-7, IL-8,
IL-2, and IL-1β) at the infected lung tissue [40, 41]. Indeed, available data suggest that this syndrome may induce self-sustaining hyper-inflammation reactions in a
sub-group of patients with severe COVID-19, leading to
respiratory and multi-organ failure [40]. Of note, hypercytokinemia and activated pro-inflammatory pathways
are also considered to promote the pathogenesis andcardio-metabolic complications of PCOS, particularly
when combined with central obesity [19, 23]. It is nowwell established that women with PCOS and obesity exhibit marked adipose tissue dysfunction and dysregulated adipokine/cytokine secretion (e.g., increased releaseof leptin, tumor necrosis factor-α, and IL-6) which resultin a chronic pro-inflammatory state [19, 23]. Furthermore,compared to healthy controls, women with PCOS seem tofrequently have polymorphisms in genes encoding proinflammatory cytokines, such as tumor necrosis factor-α
and IL-6 [42, 43]. Both the latter cytokines have also beenreported to induce theca cell steroidogenesis by upregulating
enzymes involved in ovarian androgen synthesis [19], while
ACE-2 is widely expressed in the ovary [44]. Of note, theandrogen receptor is also known to play a role in adaptive
and innate immunity, particularly in macrophage andneutrophil recruitment, which are closely linked with
COVID-19 in the lungs [40]. Therefore, it is plausible thatchronic inflammation may constitute another aspect of the
PCOS pathophysiology which may be of relevance to
COVID-19-related hyper-inflammation (Fig. 1), as has also
been suggested for diabetes [45].
Ethnic background

Recent mortality data strongly indicate that Black, Asian,and Minority Ethnic (BAME) groups are at increased riskof death from COVID-19 even after adjusting for multiple
other covariates [9, 10, 46, 47]. Indeed, an analysis of
COVID-19-related deaths by ethnic group in England andWales from the UK Office for National Statistics has
shown that the risk of COVID-19-related death is significantly higher in adults of Black, Bangladeshi and Pakistani,
Indian, and mixed ethnicities compared to that of adultsof White ethnicity [48]. Although less prominent, this risk
remained significantly increased after accounting for age
and other socio-demographic characteristics, as well as
measures of self-reported disability and health [48]. Thisfurther indicates that the difference in COVID-19
mortality between ethnic groups is only partly explainedby socio-economic disadvantage and other related parameters [48]. Notably, it has also been documented that 63%
of a series of 106 healthcare workers who have died fromCOVID-19 were of BAME background [49]. Multiple
factors are considered to contribute to the noted higher
risk of BAME groups for COVID-19 severity andPage 4 of 10

mortality, such as higher rates of the aforementioned
cardio-metabolic comorbidities and inequalities due tolower socio-economic status, as well as behavioral andcultural differences (e.g., inter-generational cohabitation
with less social distancing at households) [47, 50]. The potential role of various genetic factors in this association
has also been hypothesized, including ethnicity-related differences in genetic variations of the androgen receptor[32, 47]. In this context, it should be highlighted that substantial ethnic variation has also been documented regarding the diagnosis and presentation of PCOS [27, 51, 52].
Again significant overlap exists here with the noted ethnic
predisposition for adverse COVID-19 outcomes, with increasing data showing that particularly women of African
American, Hispanic, Middle Eastern, and South Asian origin exhibit more frequent and worse cardio-metabolic features of PCOS [27, 51, 52]. Moreover, certain IL-6
polymorphisms appear to influence PCOS susceptibility in
Caucasians, while certain tumor necrosis factor-α polymorphisms might influence PCOS susceptibility in Asians[43]. As such, clinicians should not overlook the fact thatBAME background may also be added to the overlapping
factors which promote both an unfavorable cardiometabolic profile in women with PCOS and severe
COVID-19 (Fig. 1).
Low vitamin D levels

Since COVID-19 has been declared a pandemic, potential
links between low vitamin D levels and COVID-19 severity have been hypothesized [53–61]. This was triggered by
the fact that this pandemic evolved rapidly in several
Northern hemisphere countries (e.g., Italy, Spain, France,and UK) during and shortly after winter when sun exposure and vitamin D levels are typically lowest, while
COVID-19 cases remained relatively low in the Southernhemisphere during the end of summer [55–58]. Moreover,existing evidence indicates that vitamin D deficiency cancontribute to acute respiratory distress syndrome (ARDS),
while COVID-19-related mortality increases with botholder age and cardio-metabolic comorbidity which also
exhibit positive associations with lower vitamin D levels[55–58]. Interestingly, a recent cross-sectional analysis ofdata on vitamin D levels and COVID-19 morbidity/mortality for 20 European countries showed negative correlations between mean vitamin D levels and both thenumber of COVID-19 cases and COVID-19 mortality ineach country [60]. Of note, particularly low vitamin Dlevels were noted in the aging populations of Italy andSpain, which were among the main epicenters of the
COVID-19 pandemic in Europe [60]. However, suchcross-sectional data have obvious limitations, while a recent UK Biobank-based study (data on UK Biobank participants, aged 37–73 years, of whom 449 had confirmed
COVID-19) showed that vitamin D was associated with

Kyrou et al. BMC Medicine(2020) 18:220

COVID-19 univariably, but not after adjustment for confounders [62]. Hence, this study concluded that these findings do not support a potential link between COVID-19
and vitamin D levels [62]. Nevertheless, vitamin D is awell-known pleiotropic hormone which modulates theadaptive and innate immune responses, and can regulate
the IL-6 activity and suppress the pro-inflammatory cytokine response of macrophages and respiratory epithelial
cells to various viruses [53, 54, 57, 58]. Thus, the potential
role of low vitamin D levels in COVID-19 severity and thedevelopment of a related cytokine storm syndrome merits
further well-designed research [53, 54, 57, 58]. Notably,growing data support an inverse association between vitamin D and the severity of multiple PCOS manifestations,
including hyperandrogenism, infertility, insulin resistance,and cardio-metabolic disease [63, 64]. Furthermore, metaanalysis data indicate that vitamin D supplementation in
women with PCOS might significantly decrease total testosterone and C-reactive protein circulating levels, while it
can increase the level of total antioxidant capacity [65, 66].
Taken together, these data suggest that women with
PCOS may be at potentially higher risk for severe
COVID-19 also due to low vitamin D levels (Fig. 1), which
may be further aggravated by reduced sun exposure due
to COVID-19-related quarantine measures.

Potential COVID-19-related implications on
aspects of PCOS treatment
In addition to the aforementioned frequent conditions/factors which are common in PCOS and may increase therisk for severe COVID-19 in this female patient
population, it is also important to highlight certain points
which have been the subject of discussion in the recent
scientific literature in relationship to COVID-19 andwhich also relate to aspects of PCOS treatment (Table 1).
Metformin treatment

In several countries, metformin is frequently prescribed
off-label for the management of women with PCOS andincreased BMI, even without co-existing T2DM, since it
can improve both reproductive and metabolic outcomesin these patients [19, 20]. Historically, it is noteworthy
that metformin was essentially rediscovered in the 1940s
during the search for anti-malarial agents, when it was
shown useful to treat influenza and also to lower blood
glucose as a side effect [67]. Giver the former use, it is
not surprising that metformin has been consideredamong the drugs which could be repurposed against
COVID-19, with potential antiviral effects through activation of the AMP-activated protein kinase (AMPK)
pathway that would cause changes in the ACE-2
receptor and block the entry of SARS-CoV-2 into hostcells [68]. However, metformin use can promote lactic
acidosis in the context of marked dehydration and renal

Page 5 of 10

Table 1 Potential COVID-19-related implications on aspects ofpolycystic ovary syndrome (PCOS) management (in womenwith PCOS who are diagnosed with COVID-19, a relevant risk
assessment should be performed by the treating physician andany existing treatment should be promptly re-evaluated andoptimized, as clinically indicated)
A) For women with PCOS on off-label metformin treatment: it is advisable
to consider discontinuing metformin when diagnosed with COVID-19,
particularly when symptoms of severe COVID-19 are present and if they
become unstable, as also recommended for patients with diabetesB) For women with PCOS and diabetes:- Should consider discontinuing sodium-glucose co-transporter-2
inhibitors (SGLT2i) when COVID-19 is diagnosed, particularly when
symptoms of severe COVID-19 are present- Should continue and optimize insulin therapy, as clinically indicated- Can continue the use of dipeptidyl peptidase-4 (DPP4) inhibitors
where clinically indicated (the dose of certain DPP4 inhibitors mayneed adjustment if renal function is affected in severe COVID-19)- Should consider avoiding/optimizing the use of sulfonylureas when
COVID-19 is diagnosed, particularly when symptoms of severe
COVID-19 are present, due to the risk of hypoglycemia
C) Women with PCOS and known or suspected insulin resistance (known
type 2 diabetes or prediabetes) who receive glucocorticoid treatment for
COVID-19 may exhibit overt glucocorticoid-induced glucose/metabolic
dysregulation
D) Women with PCOS and hypertension may continue treatment with
common antihypertensive drugs [angiotensin converting enzyme (ACE)inhibitors, angiotensin-receptor blockers (ARBs), thiazide diuretics,
calcium-channel blockers and beta-blockers], as indicated, since available
data so far indicate that these appear to not substantially increase therisk for testing COVID-19 positive and for severe COVID-19
E) Women with PCOS and obstructive sleep apnea (OSA) may continue
home use of continuous positive airway pressure (CPAP) therapy, but,particularly in cases of home self-isolation due suspected or confirmed
COVID-19, these patients should consider either taking strict quarantine
measures from other household members (e.g., use of separate bedrooms and bathrooms where feasible) or discontinuing CPAP therapy
for a short period, due to potential risk of SARS-CoV-2 aerosolized
transmission from the CPAP use. During any such temporary CPAP
therapy discontinuation, sedating medications and alcohol should be
avoided, while other measures to reduce OSA can also be considered,such as positional therapy during sleep, nasal congestion treatment, anddental appliance use where possible

impairment in severe COVID-19; hence, women with
PCOS under metformin treatment is advisable to consider stopping this agent when symptomatic with
COVID-19, particularly if they become unstable, as also
recommended for patients with diabetes [69–71].
Other glucose lowering medications

As with metformin, women with PCOS and diabetes
should follow the recent practical recommendations andguidelines issued for antidiabetic medications in view of
COVID-19 [69, 70]. Accordingly, due to the related riskof diabetic ketoacidosis and dehydration from sodiumglucose co-transporter-2 inhibitors (SGLT2i), discontinuing these agents should be considered when
COVID-19 is diagnosed, particularly in symptomaticpatients [69–71]. Conversely, insulin therapy should beKyrou et al. BMC Medicine(2020) 18:220

continued and optimized, while it remains the treatmentof choice for severely ill patients with diabetes and
COVID-19 [69–71]. Furthermore, the use of dipeptidyl
peptidase-4 (DPP4) inhibitors seems to be mostly welltolerated and can also be continued where indicated (thedose of certain DPP4 inhibitors may need to be adjusted
depending on whether the renal function is affected insevere COVID-19) [69–71]. Interestingly, the ubiquitously expressed membrane-associated human DPP4 appears to be a functional receptor for the Middle East
respiratory syndrome coronavirus (MERS-CoV), but not
for SARS-CoV-2 [71]. Finally, due to the related increased risk of hypoglycemia, avoiding/optimizing theuse of sulfonylureas should also be considered in patients with severe COVID-19 [71].
In the context of glucose control in women with
PCOS and IGT or T2DM, a note should also be maderegarding potential glucocorticoid treatment which isadministered in certain hospitalized COVID-19 patients[72]. Indeed, such glucocorticoid treatment for COVID19 may aggravate the glucose and metabolic homeostasis[17, 73], particularly in women with PCOS who may
have significant underlying (and often undiagnosed) insulin resistance [19, 23, 24]. As such, in these cases
treating physicians should be on high alert regarding thepotential glucocorticoid-induced glucose/metabolic dysregulation and mitigate this as indicated.
Antihypertensive medications

Given the role of ACE-2 in facilitating the entry of
SARS-CoV-2 into host cells, the use of ACE inhibitors
for hypertension treatment in the setting of COVID-19
has been another point of recent debate [74–78]. Therefore, as hypertension is also common in women with
PCOS [19, 20, 24], it is important to note that a recent
study with relevant data on five common antihypertensive
drug classes, namely ACE inhibitors, angiotensin-receptor
blockers (ARBs), thiazide diuretics, calcium-channel
blockers, and beta-blockers, showed no substantial increase in the risk for testing COVID-19 positive and forsevere COVID-19 [74]. Overall, increasing data so far
show no evidence that ACE inhibitors or ARBs increase
the risk of COVID-19, supporting current guidelines
recommending to continue the use of these drugs as indicated despite this pandemic [74–78]. Of note, additional
data from two cohorts of men and women with heart failure showed that treatment with ACE inhibitors or ARBs
was not associated with higher plasma ACE-2 [79].
Home use of continuous positive airway pressure (CPAP)
therapy

OSA exhibits high prevalence among women with
PCOS and obesity, attributed at least partly to hyperandrogenism and central adiposity, and further aggravates

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the adverse cardio-metabolic profile of these patients[19, 25, 80, 81]. As OSA may cause various degrees of
reduced arterial oxygen saturation and additional
cardio-metabolic complications, routine CPAP home
use is often indicated in women with PCOS and OSA[19, 25, 80, 81]. However, because CPAP is regarded asa high-risk aerosol-generating procedure which may increase the risk of SARS-CoV-2 transmission to otherhousehold members, routine CPAP therapy at home
has been the subject of recent debate [82–84]. Particularly for any OSA patient with suspected or confirmed
COVID-19 who is self-isolating at home, it is reasonable to consider discontinuing CPAP therapy for ashort period due to the potential risk of SARS-CoV-2
aerosolized transmission from the CPAP use to otherhousehold members [82, 85]. Alternatively, strict distancing measures within the household (e.g., changing
bedrooms and using different bathrooms where feasible) should be taken in order to protect household
contacts [82, 85]. During any period of necessary CPAP
discontinuation, OSA patients should be informed of
the related risk/consequences and avoid sedating medications and alcohol use [82]. In addition, during such
periods of temporary CPAP discontinuation, otherpractical measures to reduce OSA-related symptomatology can be also considered, such as positional therapy during sleep (head elevated at least 30° or side
sleeping), nasal congestion treatment, and dental appliance use where possible [82].

Practical recommendations for the managementof PCOS during the COVID-19 pandemic
Given the aforementioned overlap between risk factors
for severe COVID-19 and common PCOS features, andthe implications that a COVID-19 diagnosis may haveon various aspects of PCOS care, it is crucial for theclinical practice to recognize that closer monitoring andrevised management plans may be required for this female patient population during this pandemic. As such,clinicians treating women with PCOS, irrespective of
their specialty, should assess the risk profile of these patients in relationship to COVID-19. Depending on theoutcome of this risk assessment regarding coexisting comorbidities which may predispose to severe COVID-19,
relevant advice should be provided about issues such as
shielding and self-isolation, as well as practical recommendations for treatment changes/optimization likethose outlined in Table 1. For example, women with
PCOS and T2DM and/or hypertension should be informed of the potential higher risk for severe COVID19, and if diagnosed with COVID-19, their treatment
should be promptly re-evaluated and optimized, as indicated (Table 1). Further clinical input may also be required in order to apply a more individualized care planKyrou et al. BMC Medicine(2020) 18:220

for women with PCOS who may have additional management issues during this pandemic. Indeed, the rates ofcertain pregnancy complications (e.g., preterm birth,
cesarean delivery, miscarriage, gestational diabetes, andpregnancy-induced hypertension and preeclampsia) arehigher in this female patient population [86–89]. Therefore, taking into account that based on recent metaanalysis data the so far reported rates of preterm birth andcesarean delivery are higher in pregnant women with
COVID-19 (although their clinical picture may not differ
from the non-pregnant population) [90], closer antenatal
and perinatal monitoring is required in pregnant womenwith PCOS, particularly when hypertension and/or diabetes are also present. Furthermore, women with PCOS
also exhibit higher risk for mental health problems (e.g.,anxiety and depression) [19, 20]. Such problems may betriggered and/or exacerbated in the setting of the COVID19 pandemic (e.g., due to issues relating to prolonged
shielding, isolation, job insecurity, and fear of ill health)[91]. Thus, clinicians should recognize this risk in this vulnerable female patient population and offer appropriate
mental health support for prevention and treatment asneeded. Moreover, it should be mentioned that COVID19 appears to predispose to thrombosis [92, 93], and so a
COVID-19 diagnosis should also prompt heightened vigilance for potential thromboembolic complications inwomen with PCOS who may already be at increased
thrombotic risk, particularly when additional prothrombotic factors are also present (e.g., obesity, treatment with combined oral contraceptives) [94]. Finally, as
COVID-19 is a new disease which is now being studied
systematically, clinicians should keep in mind that there
may be unpredictable, longer term consequences following a SARS-CoV-2 infection which are yet unknown (e.g.,long-term dysregulation of endocrine functions and metabolic homeostasis) [95]. Therefore, follow-up of womenwith PCOS who recover from COVID-19 should also be
implemented in clinical practice in order to promptly
diagnose and treat any such potential long-term complications of COVID-19 [95].

Conclusions
At a first glance, women with PCOS appear to belong toan age and sex group which is considered as less affectedby COVID-19. However, it should be highlighted thatwithin this common female patient population there ishigh prevalence of numerous conditions/factors which
may significantly increase the risk for worse COVID-19related outcomes. This strong overlap should not be
overlooked in clinical practice, particularly since womenwith PCOS often receive fragmented care from multiple
healthcare services. In parallel, informing women with
PCOS regarding the potential risks from COVID-19 andhow this may affect their management is also necessary.

Page 7 of 10

Overall, despite the immense challenges posed by the
COVID-19 outbreak in affected countries, attention
should be directed to maintain a high standard of carefor complex patients, such as many women with PCOS,
and provide relevant practical recommendations for optimal management in the setting of this fast moving
pandemic.
Abbreviations
ACE-2: Angiotensin-converting enzyme 2; AMPK: AMP-activated protein
kinase; ARBs: Angiotensin-receptor blockers; ARDS: Acute respiratory distresssyndrome; BAME: Black, Asian, and Minority Ethnic; BMI: Body mass index;
CPAP: Continuous positive airway pressure; DHEAS: Dehydroepiandrosterone
sulphate; DPP4: Dipeptidyl peptidase-4; IGT: Impaired glucose tolerance;
IL: Interleukin; MERS-CoV: Middle East respiratory syndrome coronavirus;
NAFLD: Non-alcoholic fatty liver disease; OSA: Obstructive sleep apnea;
PCOS: Polycystic ovary syndrome; SARS-CoV-2: Severe acute respiratory
syndrome coronavirus-2; SGLT2i: Sodium-glucose co-transporter-2 inhibitors;
SHBG: Sex hormone binding globulin; T2DM: Type 2 diabetes mellitus
Acknowledgements
IK and HR acknowledge and thank the General Charities of the City ofCoventry for their support. This review is also dedicated to all of thehealthcare professionals fighting against the COVID-19 pandemic.
Authors’ contributions
IK, EK, TR, KC, FD, and HR contributed to the literature search and drafted
sections of this manuscript. IK and HR combined and edited the drafts andsupervised the manuscript. All authors subsequently revised and approved
the final manuscript.
Funding
There was no specific funding for this manuscript.
Availability of data and materials
Not applicable.
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Author details
1
Warwickshire Institute for the Study of Diabetes, Endocrinology andMetabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS
Trust, Coventry CV2 2DX, UK. 2Aston Medical Research Institute, Aston
Medical School, Aston University, Birmingham B4 7ET, UK. 3Warwick Medical
School, University of Warwick, Coventry CV4 7AL, UK. 4College of Health andLife Sciences, Brunel University London, Uxbridge UB8 3PH, UK. 5Institute of
Digital Healthcare, WMG, University of Warwick, Coventry CV4 7AL, UK.
6
Department of Biochemistry and Immunology, University Hospitals Coventry
and Warwickshire NHS Trust, Coventry CV2 2DX, UK. 7Institute ofCardiovascular Science, University College London, London, UK.
Received: 26 May 2020 Accepted: 2 July 2020

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